1Center for Molecular Oncology, Barts Cancer Institute - a Cancer Research UK Centre of Excellence, Queen Mary University of London, Barts and The London School of Medicine and Dentistry, London, UK.
2St Bartholomew's Hospital, London, UK.
3Pathology Group, Institute of Cell and Molecular Sciences, Queen Mary University of London, Barts and The London School of Medicine and Dentistry, London, UK.
Copyright © 2013 by the Korean Cancer Association
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Study | No. of patients | Tumor type | Arginine depletor | Overall survival (mo) | Response rate (best response) | Comments |
---|---|---|---|---|---|---|
Izzo et al. (2004) [98] | 19 | HCC | ADI-PEG20 phase I/II | 13.7 | 47% (CR+PR) | Low toxicity |
Glazer et al. (2010) [100] | 76 | HCC | ADI-PEG20 phase II | 15.8a) | SD only | [Arginine] plasma reduced |
Yang et al. (2010) [102] | 71 | HCC | Randomized phase II: 160 or 320 IU/m2 of ADI-PEG20 | 7.3 | 31% (SD) | PFS 1.8 mo; heavily pre-treated patients |
Yau et al.(2013) [104] | 15 | HCC | peg-rhArg1 phase I | 5.1 | 26.7% (SD) >8 wk | PFS 2.8 mo; heavily pre-treated; OBD=1,600 IU/kg; I.V. administration |
Ascierto et al. (2005) [99] | 39 | Melanoma | ADI-PEG20 phase I/II | 15 | 25% (CR+PR) | Reduced NO synthesis consistent with MOA |
Feun et al. (2012) [33] | 38 | Melanoma | ADI-PEG20 phase II |
14.6 (ASS1-ve) vs. 9.3 (ASS1+ve) (p=0.374) |
11% (PR) in ASS1-ve only | PFS 3.6 mo (ASS1-ve) vs. 1.8 mo (ASS1+ve) (p=0.025); 74% ASS1-ve frequency; ASS1 re-expression on relapse (n=2/2) |
Ott et al. (2013) [101] | 31 | Melanoma | ADI-PEG20 phase I/II | n/a | 25% Early PMR, 29% (SD) | Prolonged SD in choroidal melanoma |
Szlosarek et al. (2013) [103,105] | 68 | Mesothelioma | Randomized phase II in ASS1-ve patients: ADI- PEG20+BSC (n=44) vs. BSC alone (n=24) | n/a | 46% Early PMR, SD by modified RECIST | PFS 3.3 mo vs. 1.9 mo (p=0.02) favoring ADI-PEG20+BSC; ASS1 methylation status correlated with IHC (p=0.025) |
HCC, hepatocellular carcinoma; CR, complete response; PR, partial response; SD, stable disease; PFS, progression-free survival; NO, nitric oxide; MOA, mechanism of action; ASS1, argininosuccinate synthetase 1; n/a, not available; PMR, partial metabolic response; OBD, optimal biological dose; BSC, best supportive care; RECIST, Response Evaluation Criteria in Solid Tumors; IHC, immunohistochemistry. a)From diagnosis.
Study | No. of patients | Tumor type | Arginine depletor | Overall survival (mo) | Response rate (best response) | Comments |
---|---|---|---|---|---|---|
Izzo et al. (2004) [98] | 19 | HCC | ADI-PEG20 phase I/II | 13.7 | 47% (CR+PR) | Low toxicity |
Glazer et al. (2010) [100] | 76 | HCC | ADI-PEG20 phase II | 15.8 |
SD only | [Arginine] plasma reduced |
Yang et al. (2010) [102] | 71 | HCC | Randomized phase II: 160 or 320 IU/m2 of ADI-PEG20 | 7.3 | 31% (SD) | PFS 1.8 mo; heavily pre-treated patients |
Yau et al.(2013) [104] | 15 | HCC | peg-rhArg1 phase I | 5.1 | 26.7% (SD) >8 wk | PFS 2.8 mo; heavily pre-treated; OBD=1,600 IU/kg; I.V. administration |
Ascierto et al. (2005) [99] | 39 | Melanoma | ADI-PEG20 phase I/II | 15 | 25% (CR+PR) | Reduced NO synthesis consistent with MOA |
Feun et al. (2012) [33] | 38 | Melanoma | ADI-PEG20 phase II | 14.6 (ASS1-ve) vs. 9.3 (ASS1+ve) (p=0.374) |
11% (PR) in ASS1-ve only | PFS 3.6 mo (ASS1-ve) vs. 1.8 mo (ASS1+ve) (p=0.025); 74% ASS1-ve frequency; ASS1 re-expression on relapse (n=2/2) |
Ott et al. (2013) [101] | 31 | Melanoma | ADI-PEG20 phase I/II | n/a | 25% Early PMR, 29% (SD) | Prolonged SD in choroidal melanoma |
Szlosarek et al. (2013) [103,105] | 68 | Mesothelioma | Randomized phase II in ASS1-ve patients: ADI- PEG20+BSC (n=44) vs. BSC alone (n=24) | n/a | 46% Early PMR, SD by modified RECIST | PFS 3.3 mo vs. 1.9 mo (p=0.02) favoring ADI-PEG20+BSC; ASS1 methylation status correlated with IHC (p=0.025) |
Study | Clinical Trials. Gov Identifier | No. of patients | Tumor type | Biomarker | Lead site |
---|---|---|---|---|---|
Docetaxel and ADI-PEG20 | NCT01497925 | 39 | Prostate NSCLC | Retrospective ASS1 | University of California at Davis, CA |
Cisplatin and ADI-PEG20 | NCT01665183 | 61 | Solid tumors including metastatic melanoma | ASS1-deficient ADI-PEG20 | MD Anderson, TX |
Doxorubicin and ADI-PEG20 | NCT01948843 | 53 | Breast cancer | ASS1-deficient (>75% cells) HER2 negative | MD Anderson, TX |
Cisplatin, pemetrexed and ADI-PEG20 | To be determined | 37 | NSCLC (adeno) malignant pleural mesothelioma | ASS1-deficient (>50% cells) FLT-PET/CT imaging | Barts, London, UK |
HCC, hepatocellular carcinoma; CR, complete response; PR, partial response; SD, stable disease; PFS, progression-free survival; NO, nitric oxide; MOA, mechanism of action; ASS1, argininosuccinate synthetase 1; n/a, not available; PMR, partial metabolic response; OBD, optimal biological dose; BSC, best supportive care; RECIST, Response Evaluation Criteria in Solid Tumors; IHC, immunohistochemistry. a)From diagnosis.
NSCLC, non-small cell lung cancer; ASS1, argininosuccinate synthetase 1; FLT, 18F-fluorothymidine; PET/CT, positron emission tomography/computed tomography.